电压激活的钾通道阻断剂抑制山莨菪碱松弛去甲肾上腺素预收缩的兔主动脉平滑肌  

Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline

作　　者：刘书勤[1] 臧伟进[1] 李增利[1] 孙强[1] 于晓江[1] 罗宏丽 朱树明[1] 

机构地区：[1]西安交通大学医学院药理学教研室,西安710061

出　　处：《生理学报》2005年第1期21-26,共6页Acta Physiologica Sinica

基　　金：This work was supported by the National Natural Science Foundation of China (No. 30270554) Key Item of Scientific Technol- ogy for Ministry of Education (No.01161)Natural Science Foundation of Xi'an Jiaotong University (No. 573021)

摘　　要：研究显示,山莨菪碱预处理不改变高钾引起的兔主动脉环收缩,但可明显减弱去甲肾上腺素(noradrenaline,NA)、组织胺或5-羟色胺引起的收缩,且其减弱作用不受去除血管内皮影响。本实验观察了几种钾通道阻断剂对山莨菪碱松弛NA预收缩的兔主动脉环的影响。结果表明,1、3、10μmol/L山莨菪碱作用8min,可使0.01μmol/LNA预收缩的兔主动脉环松弛(P<0.01)。10mmol/LCsCl、1mmol/L4-氨基吡啶、10μmol/LBaCl2、10μmol/L格列本脲、3μmol/Lcharybdotoxin和3μmol/L蜂毒明肽分别与O.01μmol/LNA同时加入,可增强后者收缩兔主动脉环的作用(P<0.01)。10、30mmol/LCsCl或10、30mmol/L4-氨基吡啶存在时,10μmol/L山莨菪碱对NA预收缩的兔主动脉环的松弛作用减弱,松弛率与对照组比较分别有极显著差异(P<0.01);10、30μmol/LBaCl2,10、30μmol/L格列本脲,3μmol/Lcharybdotoxin或3μmol/L蜂毒明肽存在时,山莨菪碱对NA预收缩的兔主动脉环的松弛作用不受影响(P>0.05)。本研究表明,电压激活的钾通道阻断剂抑制山莨菪碱松弛NA预收缩的兔主动脉平滑肌,初步提示血管平滑肌细胞膜上电压激活的钾通道参与山莨菪碱扩血管作用。Anisodamine, which is originally extracted from scopolia tangutica and is currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor blocker. Our previous study found that anisodamine did not alter high K+-evoked contraction of rabbit aortic rings using isometric tension recording methods, but could attenuate noradrenaline (NA)-, histamine- or 5-hydroxytryptamine-induced contraction in an endothelium-independent manner. Since the high K+-elicited depolarization non-selectively inhibits potassium channels in vascular smooth muscle cell (VSMC) membrane, the vasodilation effect of some potassium channel activators may be inhibited or abolished in high K+ solution. We hypothesized that some potassium channels in VSMC membrane might play a role in the anisodamine-induced relaxation of blood vessels. The present experiment was designed to investigate whether potassium channel blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic rings. In a 8-min period, 1, 3 and 10 μmol/L of anisodamine, significantly relaxed the 0.01 umol/L NA precontracted aortic ring by (19.1±3.1)%, (30.1±3.8)% and (38.3±4.2)%, respectively, compared with the controls [by (4.8±2.4)%, (5.1±1.8)% and (5.6±2.5)%, respectively] (P<0.01). 10 mmol/L of CsCl (a non-selective potassium channel blocker), 1 mmol/L of 4-aminopyridine [a selective voltage-activated potassium channel (Kv) blocker], 10 μmol/L BaCl2 (a selective inwardly-rectifying potassium channel blocker), 10 μmol/L of glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 μmol/L of charybdotoxin (a large- and intermediate-conductance Ca2+-activated potassium channels blocker) and 3 μmol/L of apamin (a selective small conductance Ca2+-activated potassium channel blocker) significantly increased the NA-induced contraction by (14.4±3.2)%, (16.3±5.8)%, (12.7±4.2)%, (13.6±2.0)%, (11.1±5.5)% and (13.4±4.3)%, respectively, compared with the control [by (5.6±+1.2)%] (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1

关 键 词：钾通道 电压激活的钾通道 山莨菪碱 家兔 主动脉 去甲肾上腺素 

分 类 号：R96[医药卫生—药理学]